Secondary Anterior Cruciate Ligament Injury Prevention Training in Athletes: What Is the Missing Link?

After reconstruction, the return to full competition rate of athletes is low, while the re-injury rate remains high despite the completion of a rehabilitation programme. Primary ACL prevention programmes are well developed, yet few research papers focus on secondary ACL injury prevention. The aim of current review is to determine if current ACL secondary prevention training has a positive influence on the re-injury rate, the clinical or functional outcomes, or the risk of re-injury in athletes. Studies investigating secondary prevention of ACL were searched in PubMed and EBSCOhost, followed by a review of the references in the identified articles. The existing evidence suggests that neuromuscular training, eccentric strengthening, and plyometric exercises may have a potential impact on improving biomechanical, functional, and psychological outcomes in athletes; however, the studies on the prevention of second ACL injury in athletes is scarce and inconclusive. Future research is needed to investigate the effectiveness of secondary ACL prevention in reducing the re-injury rates. (PROSPERO Registration number: CRD42021291308).

Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement.

Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.

Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice.

INTRODUCTION: We previously demonstrated that magnesium ions (Mg2+) was a novel therapeutic alternative for osteoarthritis (OA) through promoting the hypoxia inducible factor-1α (HIF-1α)-mediated cartilage matrix synthesis. However, oxidative stress can inhibit the expression of HIF-1α, amplify the inflammation that potentially impairs the therapeutic efficacy of Mg2+ in OA. Vitamin (VC), a potent antioxidant, may enhance the efficacy of Mg2+ in OA treatment. This study aims to investigate the efficacy of combination of Mg2+ and VC on alleviating joint destruction and pain in OA. MATERIAL AND METHODS: Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline, MgCl2 (0.5 mol/L), VC (3 mg/ml) or MgCl2 (0.5 mol/L) plus VC (3 mg/ml) at week 2 post-operation, twice weekly, for 2 weeks. Joint pain and pathological changes were assessed by gait analysis, histology, western blotting and micro-CT. RESULTS: Mg2+ and VC showed additive effects to significantly alleviate the joint destruction and pain. The efficacy of this combined therapy could sustain for 3 months after the last injection. We demonstrated that VC enhanced the promotive effect of Mg2+ on HIF-1α expression in cartilage. Additionally, combination of Mg2+ and VC markedly promoted the M2 polarization of macrophages in synovium. Furthermore, combination of Mg2+ and VC inhibited osteophyte formation and expressions of pain-related neuropeptides. CONCLUSIONS: Intra-articular administration of Mg2+ and VC additively alleviates joint destruction and pain in OA. Our current formulation may be a cost-effective alternative treatment for OA.

The 3D-Printed PLGA Scaffolds Loaded with Bone Marrow-Derived Mesenchymal Stem Cells Augment the Healing of Rotator Cuff Repair in the Rabbits.

The healing of tendon-bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs-PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs-PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs-PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon-bone interface. The biomechanical analysis showed that BMSCs-PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon-bone healing in the rabbit rotator cuff repair model.

The effect of thermosensitive hydrogel platelet-rich-plasma complex in the treatment of partial tear of anterior cruciate ligament in rat model.

BACKGROUND/OBJECTIVE: The treatment of anterior cruciate ligament (ACL) partial tear is controversial. The reconstructive surgery is invasive while the prevalence of subsequent insufficiency after conservative treatment has been reported to range from 11% to 62%. Therefore, a new method that promotes tissue regeneration is needed. The aim of this study was to observe the healing of ACL partial tear biomechanically and histologically after the administration of a thermosensitive hydrogel platelet-rich-plasma (PRP) complex. METHODS: The complex was prepared according to a previously published protocol. One hundred and fifty 12-week-old male Sprague-Dawley rats were included and they were allocated into 4 groups. Lesion control group (Group 1), treatment group (Group 2), gel-only group (Group 3) and intact group (Group 4). Biomechanical testing, histological analysis (H&E and immunohistochemical staining) and scoring was performed. RESULTS: On gross observation, the treatment group showed a continuous ACL with slightly thickened synovium or a partially healed ACL at 6-week follow up. In the biomechanical testing at 6 weeks after surgery, the failure load of the treatment group was significantly superior when compared with the lesion control group (52.7±10.8N vs. 41.6±7.8N, p<0.01), but the failure load was not restored to level of the intact group (52.7±10.8N vs. 61.5±9.1N, p=0.037). The maturity index of wound sites showed no significant inter-group differences at any timepoints. However, an increased expression of vascular endothelial growth factor (VEGF) and pro-collagen I was detected. CONCLUSION: The thermosensitive hydrogel-PRP was shown to be effective in enhancing the healing of ACL partial tear in the rat model, and potentially this complex can be used as a treatment for patients with ACL partial tear. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The thermosensitive hydrogel-PRP is potentially translated to clinical use to treat patients with ACL partial tear by injection under arthroscopy or ultrasound guiding.

Prevalence of patellofemoral joint osteoarthritis after anterior cruciate ligament injury and associated risk factors: A systematic review.

BACKGROUND: The prevalence of patellofemoral joint (PFJ) osteoarthritis (OA) after anterior cruciate ligament (ACL) injury was inconsistently reported in the literature. This review summarises the reported prevalence of PFJ OA and risk factors of PFJ OA after ACL injury. METHODS: PubMed, Embase, WoS, and MEDLINE (OVID) were searched up to 1 March 2019. A modified version of the Coleman methodology score was used to assess the methodological quality of the included studies. Prevalence of PFJ OA was pooled depended on different interventions in ACL injured populations. RESULTS: Thirty-eight studies were included. Five different radiographic classification methods were used: the Kellgren and Lawrence Grade 2, IKDC Grade B, Fairbank Grade 1, joint space narrowing of Grade 2 based on OARSI, and Ahlbäck Grade 1. One included study used MRI Osteoarthritis Knee Score to evaluate PFJ degenerative changes. The overall prevalence of PFJ OA after ACL injury in included studies varied between 4.5% and 80%. The large variation of PFJ OA prevalence is mainly because of different follow-up period and surgical techniques. The pooled data showed that bone-patellar tendon-bone graft, single-bundle ACL reconstruction (ACLR), and delayed ACLR are likely associated with PFJ degenerative changes after ACL injury. ACLR, delayed ACLR, body mass index (BMI), meniscectomy, patellofemoral chondral lesions, age at surgery, and TFJ OA were identified in the literature inducing PFJ OA after ACL injury. CONCLUSIONS: Large variations of PFJ OA after ACL injury are associated with different follow-up period and surgical techniques. ACL reconstructed population with bone-patellar tendon-bone graft, single-bundle reconstruction, and delayed operation time has a high prevalence of PFJ OA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This review focuses more on the effect of surgical technique factors on the degenerative changes on PFJ. The results reveal that BPTB, single-bundle reconstruction, and delayed ACLR are more likely associated with PFJ degenerative changes after ACL injury. These findings imply that awareness of PFJ problems after surgical intervention will remind of surgeons taking PFJ into consideration in operations, which is likely to reduce the incidences of anterior knee pain, patellar maltracking, and over-constrained patella in the early stage after surgery.

Intra-Articular Delivery of Quercetin Using Thermosensitive Hydrogel Attenuate Cartilage Degradation in an Osteoarthritis Rat Model.

OBJECTIVE: Quercetin (Que), a bioflavonoid, is both anti-inflammatory and antioxidative. Que has been used as an oral supplement for osteoarthritis (OA) with inconsistent findings because of its low bioavailability. We encapsulated Que in a mPEG-polypeptide thermogel to prolong its bioactivity. The efficacy of this formulation was evaluated in a posttraumatic OA rat model. DESIGN: Methoxy-poly(ethylene glycol)-l-poly(alanine) (mPEG-PA) polymer was synthesized and characterized in terms of cytotoxicity and release kinetics in vitro. At 12 weeks old, Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT). At 24 weeks post-operation, rats received either an intra-articular (IA) injection of saline, hydrogel, or hydrogel with Que (50 or 500 µg). Gait analysis was performed at pre-ACLT, pre-treatment, and at 4, 8, and 12 weeks post-treatment. At 12 weeks post-treatment, knee joints were collected for histopathological evaluation. RESULTS: In vitro studies showed that chondrocytes were viable after 72 hours of incubation with mPEG-PA, and the release of Que could be sustained for >28 days. Among all OA rats, the limb idleness index (LII) were significantly increased at 24 weeks post-ACLT. Rats that received hydrogel with Que (50 µg) showed the most reduction in LII at both 4 and 8 weeks post-treatment. The Osteoarthritis Research Society International score of rats received hydrogel with Que (50 µg) was significantly lower than the control group. All rats suffered from low-grade synovitis (Krenn score: 2-4). CONCLUSION: This study suggests that a sustained delivery of Que (50 µg) could provide symptom relief and also delay the progression of OA in the knee.

Impact of Platelet-Rich Plasma Use on Pain in Orthopaedic Surgery: A Systematic Review and Meta-analysis.

CONTEXT: Amid extensive debate, evidence surrounding the use of platelet-rich plasma (PRP) for musculoskeletal injuries has rapidly proliferated, and an overall assessment of efficacy of PRP across orthopaedic indications is required. OBJECTIVES: (1) Does PRP improve patient-reported pain in musculoskeletal conditions? and (2) Do PRP characteristics influence its treatment effect? DATA SOURCES: MEDLINE, EMBASE, Cochrane, CINAHL, SPORTDiscus, and Web of Science libraries were searched through February 8, 2017. Additional studies were identified from reviews, trial registries, and recent conferences. STUDY SELECTION: All English-language randomized trials comparing platelet-rich therapy with a control in patients 18 years or older with musculoskeletal bone, cartilage, or soft tissue injuries treated either conservatively or surgically were included. Substudies of previously reported trials or abstracts and conference proceedings that lacked sufficient information to generate estimates of effect for the primary outcome were excluded. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: All data were reviewed and extracted independently by 3 reviewers. Agreement was high between reviewers with regard to included studies. RESULTS: A total of 78 randomized controlled trials (5308 patients) were included. A standardized mean difference (SMD) of 0.5 was established as the minimum for a clinically significant reduction in pain. A reduction in pain was associated with PRP at 3 months (SMD, -0.34; 95% CI, -0.48 to -0.20) and sustained until 1 year (SMD, -0.60; 95% CI, -0.81 to -0.39). Low- to moderate-quality evidence supports a reduction in pain for lateral epicondylitis (SMD, -0.69; 95% CI, -1.15 to -0.23) and knee osteoarthritis (SMD, -0.91; 95% CI, -1.41 to -0.41) at 1 year. PRP characteristics did not influence results. CONCLUSION: PRP leads to a reduction in pain; however, evidence for clinically significant efficacy is limited. Available evidence supports the use of PRP in the management of lateral epicondylitis as well as knee osteoarthritis.

The non-reconstructive treatment of complete ACL tear with biological enhancement in clinical and preclinical studies: A systematic review.

INTRODUCTION: There is still controversy regarding the bio-enhanced non-reconstructive ACL treatment. MATERIALS AND METHODS: A search for articles in databases was performed in February 2017. The objective and subjective evaluations of clinical studies and biomechanical and histological data of preclinical studies were extracted. RESULTS: Eighteen articles were included for analysis. In clinical studies, although subjective scores were significantly improved, the rate of re-operation rate was high. In preclinical studies, bio-enhancing techniques demonstrated promotion of the healing of ACL. CONCLUSIONS: The efficacy of biological enhancement cannot be validated in clinical studies. Preclinical studies showed improved biomechanical and healing potential.

Presence of Bacteria in Spontaneous Achilles Tendon Ruptures.

BACKGROUND: The structural pathology of Achilles tendon (AT) ruptures resembles tendinopathy, but the causes remain unknown. Recently, a number of diseases were found to be attributed to bacterial infections, resulting in low-grade inflammation and progressive matrix disturbance. The authors speculate that spontaneous AT ruptures may also be influenced by the presence of bacteria. HYPOTHESIS: Bacteria are present in ruptured ATs but not in healthy tendons. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with spontaneous AT ruptures and patients undergoing anterior cruciate ligament (ACL) reconstruction were recruited for this study. During AT surgical repair, excised tendinopathic tissue was collected, and healthy tendon samples were obtained as controls from hamstring tendon grafts used in ACL reconstruction. Half of every sample was reserved for DNA extraction and the other half for histology. Polymerase chain reaction (PCR) was conducted using 16S rRNA gene universal primers, and the PCR products were sequenced for the identification of bacterial species. A histological examination was performed to compare tendinopathic changes in the case and control samples. RESULTS: Five of 20 AT rupture samples were positive for the presence of bacterial DNA, while none of the 23 hamstring tendon samples were positive. Sterile operating and experimental conditions and tests on samples, controlling for harvesting and processing procedures, ruled out the chance of postoperative bacterial contamination. The species identified predominantly belonged to the Staphylococcus genus. AT rupture samples exhibited histopathological features characteristic of tendinopathy, and most healthy hamstring tendon samples displayed normal tendon features. There were no apparent differences in histopathology between the bacterial DNA-positive and bacterial DNA-negative AT rupture samples. CONCLUSION: The authors have demonstrated the presence of bacterial DNA in ruptured AT samples. It may suggest the potential involvement of bacteria in spontaneous AT ruptures.

A Systematic Review of Anterior Cruciate Ligament Femoral Footprint Location Evaluated by Quadrant Method for Single-Bundle and Double-Bundle Anatomic Reconstruction.

PURPOSE: To unravel the standard position of anterior cruciate ligament (ACL) femoral origin and deduce practical arthroscopic localization and postsurgical evaluation method. METHODS: Two independent reviewers searched PubMed using the terms ACL, footprint, femur, etc. We included studies published since January 1, 2000, in which the results were measured by Bernard's quadrant method. This method consists of 4 distances, including total diameter of lateral condyle along Blumensaat's line (distance t), maximum intercondylar notch height (distance h), distance from center of footprint to proximal border (distance x), and distance from center of footprint to Blumensaat's line (distance y). The data of included studies were combined to calculate theoretical centers and standard area for both ACL as a whole bundle and as anteromedial (AM) and posterolateral (PL) bundles individually. Finally, we translated the combined data to arthroscopic localization and postsurgical evaluation. RESULTS: A total of 13 studies were included. The theoretical centers of ACL as a whole bundle is 28.4% ± 5.1% (x) of distance t and 35.7% ± 6.9% (y) of distance h, whereas AM bundle is 24.2% ± 4%, 21.6% ± 5.2% (x, y) and PL bundle is 32.8% ± 4.7%, 46.7% ± 4.9% (x, y), respectively. The standard area of ACL footprint is a circle with a center of 27.53%, 35.85% (x, y), and a radius of 4.58%, 9.2% (x, y), respectively. Translation of combined data shows that under arthroscopy, for single-bundle ACL reconstruction, the midpoint of distance from border of proximal to distal articular cartilage is the center of anatomic femoral socket. CONCLUSIONS: Combined data unravel the standard position of ACL femoral origin. It can be used by clinicians to localize anatomic tunnel both in surgery and postsurgical evaluation. For single-bundle ACL reconstruction, the midpoint of lateral femoral condyle corresponds to anatomic socket. LEVEL OF EVIDENCE: Level V, systematic review of anatomic studies.

Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction.

After anterior cruciate ligament reconstruction (ACLR), the biological healing of the graft is a rate-limiting step which can contribute to graft failure. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu) is a well-known activator of tissue remodeling. We investigated whether GHK-Cu can improve graft healing following ACLR. Seventy-two rats underwent unilateral ACLR were randomized to saline, 0.3 or 3 mg/ml GHK-Cu groups (n = 24). Post-operational intra-articular injections were given from week 2, once a week, for 4 weeks. Gait analysis was performed pre-injury and at harvesting time. At 6 or 12 weeks post-operation, knee specimens were harvested for knee laxity test, graft pull-out test, and histology. At 6 weeks post-ACLR, GHK-Cu groups resulted in a smaller side-to-side difference in knee laxity as compared to the saline group (p = 0.009), but there was no significant difference at 12 weeks post-operation. The graft complex in the 0.3 mg/ml GHK-Cu group had higher stiffness than saline group at 6 weeks post-operation (p = 0.026), but there was no significant difference in ultimate load, gait parameters, and histological scores among treatment groups. All grafts failed mid-substance during pull-out test. Intra-articular supplementation with a bioactive small molecule GHK-Cu improved graft healing following ACLR in rat, but the beneficial effects could not last as treatment discontinued.

Systematic Review of Biological Modulation of Healing in Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Whether biological modulation is effective to promote healing in anterior cruciate ligament (ACL) reconstruction remains unclear. PURPOSE: To perform a systematic review of both clinical and experimental evidence of preclinical animal studies on biological modulation to promote healing in ACL reconstruction. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A systematic search was performed using the PubMed, Ovid, and Scopus search engines. Inclusion criteria were clinical and animal studies involving subjects with ACL injury with the use of biological modulation to promote healing outcomes. Methodological quality of clinical studies was evaluated using the Critical Appraisal Skill Programme (CASP) appraisal tool, and animal studies were evaluated by a scoring system based on a published checklist of good animal studies. RESULTS: Ten clinical studies and 50 animal studies were included. Twenty-five included studies were regarded as good quality, with a methodological score ≥5. These studies suggested that transforming growth factor-beta (TGF-ß), mesenchymal stem cells, osteogenic factors, and modalities that reduce local inflammation may be beneficial to promote graft healing in ACL reconstruction. CONCLUSION: This systematic review suggests that biological modulation is able to promote healing on top of surgical treatment for ACL injuries. This treatment strategy chiefly works through promotion of healing at the tunnel-graft interface, but the integrity of the intra-articular midsubstance of the graft would be another target for biological modulation.

Effect of graft tensioning on mechanical restoration in a rat model of anterior cruciate ligament reconstruction using free tendon graft.

PURPOSE: Initial graft tensioning is important in anterior cruciate ligament reconstruction (ACLR), but its effect on graft healing is still not clear. Since all previous animal studies on graft tensioning used bone-patellar tendon-bone, this study aimed to investigate the effect of initial graft tensioning on ACLR using tendon graft. METHODS: Fifty-five Sprague-Dawley rats underwent ACLR using flexor digitorum longus tendon graft. A constant force of 2 or 4 N was applied during graft fixation. At 0, 2, and 6 weeks, knee samples were harvested (n = 6) for static knee laxity test and graft pull-out test. Histological examination was performed at 2 and 6 weeks post-injury (n = 4). RESULTS: At time zero, knee laxity was restored by ACLR with 2 or 4 N tensioning as compared to ACL-deficient group (p < 0.001), and the 4 N group exhibited a better restoration as compared to 2 N group (p = 0.031). At week 2 post-operation, the 4 N group still exhibited a better restoration in knee laxity (p = 0.001) and knee stiffness (p = 0.002) than the 2 N group; the graft pull-out force (p = 0.032) and stiffness (p = 0.010) were also higher. At week 6 post-operation, there was no significant difference between the 2 and 4 N group in knee laxity and graft pull-out strength. Histological examination showed that the beneficial effect of higher initial graft tension may be contributed by maintenance of graft integrity at mid-substance and reduction in adverse peri-graft bone changes in the femoral tunnel region. CONCLUSIONS: A higher initial graft tension favours the restoration of knee laxity and promotes graft healing in ACLR using free tendon graft in the rat model.

Early failure of smooth hydroxyapatite-coated press-fit acetabular cup--7 years of follow-up.

The early results of smooth hydroxyapatite-coated press-fit acetabular cup are comparable to porous-coated press-fit cup, but these results deteriorate dramatically after 5 years. In this study, 66 primary total hip arthroplasties performed between 1994 and 1998 were reviewed. The average follow-up was 6.5 years. Of the 66 arthroplasties, 8 acetabular cups were revised for aseptic loosening presenting as rapid change of cup position. The average duration of symptoms before revision was 3 months. The survival of the cups at 5 and 9 years were 95.4% and 83%, respectively. The rapid clinical deterioration after 5 years may be due to lack of bone ingrowth into the cup making it unable to resist the shearing stress in the acetabulum. Radiolucent line was not an accurate sign for the detection of mechanical failure.